• Binu Tharakan, Robert Corprew, Felicia A Hunter, J Greg Whaley, W Roy Smythe, and Ed W Childs.
• Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Temple, TX, USA.
• Am. J. Surg. 2009 Feb 1; 197 (2): 147-54.

BackgroundPrevious work from our laboratory demonstrated the involvement of "intrinsic" mitochondrial apoptotic signaling in vascular hyperpermeability. The objective of this study was to determine if 17beta-estradiol, a known inhibitor of apoptosis, would attenuate microvascular endothelial cell hyperpermeability.MethodsRat lung microvascular endothelial cell monolayers were treated with 17beta-estradiol or estrogen-receptor antagonist ICI 182780 after transfection with BAK peptide (5 microg/mL). Fluorescein isothiocyanate (FITC)-albumin was used to determine the change in permeability. Mitochondrial reactive oxygen species (ROS) formation and transmembrane potential were determined using 123 dihydrorhodamine and JC-1, respectively. Cytosolic cytochrome c levels and caspase-3 activity were determined using enzyme-linked immunosorbent assay and fluorometric assay respectively.Results17beta-estradiol (10 nm) attenuated BAK-induced hyperpermeability (P < .05), ROS formation, cytochrome c release, and caspase-3 activation. The estrogen receptor antagonist ICI 182780 blocked the protective effect of 17beta-estradiol on hyperpermeability (P < .05).Conclusions17beta-estradiol attenuates BAK-induced hyperpermeability in rat lung microvascular endothelial cells by way of an estrogen-receptor mediated pathway.

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